The addition of photosensitizing (light-activated) compounds to blood products has been suggested as a method for the inactivation of blood-borne viruses. The screening of one such compound, the lipophilic dye merocyanine 540 (MC), for its antiviral activity has been performed with surrogate viruses. We studied the photoinactivation.of four bacteriophage, 0X174, T7, PRD1 and 06, by MC (15 micro-g/ml) and light (450-600nm, 4-10 mW/cm^2). 06 has a lipid envelope, PRD1 has internal lipid and 0X174 and T7 do not contain lipid. In addition, the feasibility of substituting surrogate viruses in screening assays for the actual human viruses transmitted by blood was examined by comparing the kinetics of inactivation of the bacteriophages with those of herpes simplex virus (HSV). The survival curves indicated different sensitivities to photoinactivation by MC, with 06 (D(0)=0.15J/cm2) being the most sensitive, followed by T7 which was 21 -fold less sensitive (D(0) =3.1 J/cm2). Although both PRD 1 and 06 have lipid components, only 06 was photoinactivated by MC. The internal lipid components of PRD 1 were not sufficient to allow photoinactivation by MC (15 ug/mL, 3.1 J/cm2). We also photoinactivated HSV (D = 0.005 J/cm) and found it to be about 30-fold more sensitive than 06 to photoinactivation. Thus, while 06 may be used as a surrogate for enveloped viruses to study photoinactivation by lipophilic dyes, the results may be only useful qualitatively. This work was presented at the meeting of the International Photodynamic Association (July, 1990) and has been submitted to Photochemistry and Photobiology (August, 1990).